The Vanderbilt Program in Drug Discovery (VPDD) is a world class effort fully focused on discovery and characterization of novel molecules to evaluate new potential treatment strategies for CNS disorders. The VPDD has had tremendous success in discovery of multiple ligands for CNS neurotransmitter receptors, ion channels, and other signaling proteins. This provides an exciting opportunity to realize unprecedented advances in understanding of the impact of manipulating these signaling pathways on animal behavior and the potential therapeutic utility of drugs acting on these systems. However, it is critical that molecules generated from this and similar academic drug discovery efforts are fully characterized in terms of pharmacokinetic properties and brain penetration before using novel molecules for in vivo studies. Thus, in vivo neuropharmacologists working with newly discovered compounds must seamlessly incorporate studies of drug disposition into their work. VPDD has established state of the art facilities for animal dosing, plasma and csf collection, and analytical chemistry required for detailed pharmacokinetic studies of novel compounds in animal models. In addition both the VPDD and Vanderbilt's Center for Molecular Neuroscience (CMN) have established outstanding facilities for use in behavioral and other in vivo studies in rodent models. This provides the opportunity to move beyond cellular and molecular studies that drive many of the current VPDD efforts and focus on gaining new insights into in vivo effects of manipulating specific neurotransmitter systems and signaling pathways. However, to take advantage of this unique opportunity, it will be critical to recruit faculty who have strong in vivo pharmacology expertise and who have the skills required to combine behavioral pharmacology with studies of drug disposition and CNS exposure of novel compounds. We now seek funding through the NIH to support recruitment of an outstanding in vivo neuropharmacologist to a tenure track faculty position in VPDD and Department of Pharmacology, we propose a strong development package to the new faculty recruit and provide a clear plan to work with new recruit to through faculty mentoring, collaborative research opportunities, and other support needed to allow the new recruit to establish an independent career and leadership position in neuropharmacology. PUBLIC HEALTH RELEVANCE: We propose recruitment of an outstanding in vivo neuropharmacologist to a tenure track faculty position in the Vanderbilt Program in Drug Discovery and the Vanderbilt Department of Pharmacology. Working within the context of the VPDD, provides a unique opportunity for an in vivo neuropharmacologist to achieve unprecedented advances in understanding of the impact of manipulating specific signaling pathways on animal behavior and the potential therapeutic utility of drugs acting on these systems. Using support from this grant, we will provide strong development package, focused faculty mentoring, collaborative research opportunities, and other support needed to help the new recruit to establish an independent career and leadership position in neuropharmacology.